Over the past several years we have studied enzyme inactivation which is catalyzed by a variety of mixed function oxidation (MFO) systems. Many of the enzymes which we have found are inactivated by MFO systems in vitro have been found by others to accumulate in inactive or less active forms during aging. Levine has shown that E. coli glutamine synthetase and other key metabolic enzymes which are oxidatively modified in vitro by MFO systems generate a carbonyl protein derivative which becomes labeled when reduced with sodium borotritide or forms a stable hydrazone when treated with 2,4-dinitrophenylhydrazine (DNPH). We have used this property to develop reagents and presumptive screening assays for the presence of oxidatively modified proteins in cell extract preparations. We have chosesn the human erythrocyte as a model for aging. It is well known the human erythrocytes are present in peripheral circulation for approximately 120 days and over that time period erythrocytes exhibit age related changes, such as a decrease in the specific activity of some enzymes. We have fractionated erythrocytes according to age (density) and we have found that the decrease in the specific activity of some enzymes in accompanied by an increase in the level of oxidatively modified protein.